Film-shaped, dissolvable preparations for active substance release and method for the production thereof

ABSTRACT

A film-shaped preparation disintegratable in aqueous media for administration of substances to the human or animal body. The preparation contains at least one water-soluble polymer. The preparation contains one or more components that produce a gas upon action of moisture, being in the presence of an aqueous medium or by a temperature change.

BACKGROUND OF THE INVENTION CROSS REFERENCE TO RELATED APPLICATIONS

This application is a National Stage application of InternationalApplication No. PCT/EP03/04806, filed on May 8, 2003, which claimspriority of German application number 102 24 607.6, filed on Jun. 4,2002.

1. Field of the Invention

The invention relates to film-shaped preparations which aredisintegratable in aqueous media and which are produced on the basis ofwater-soluble polymers and can be used for administering substances tothe human or animal body. The invention further relates to processes forthe production of such preparations as well as to the use thereof aspharmaceutical administration forms.

2. Description of the Prior Art

Flat-shaped administration forms, especially oral administration forms,which disintegrate in an aqueous environment and enable a quick releaseof active substances in the oral cavity or in other apertures orcavities of the body are already known. Such administration forms can beconfigured in the form of “wafers”, for example. Due to their smalllayer thickness and disintegratability or dissolvability thesefilm-shaped, flat administration forms are particularly suitable for thequick release of medicaments and other active substances in the oralcavity.

Flat-shaped, wafer-like films for delivering substances to the human oranimal body are as a rule made of film-forming, water-soluble polymers.When these wafers come into contact with water or with a body fluid(e.g. saliva), the polymers dissolve, thus releasing the activesubstance. The quicker the aqueous liquid reaches the inner regions ofthe wafer, the quicker the wafer disintegrates. Therefore, thedisintegration rate decreases with increasing layer thickness.

The thickness of such systems is in turn determined to a large extent bythe amount and type of the active substance to be guided. Thick wafershave the unpleasant property of sticking to the palate because of theirflat shape and their retarded disintegration. This is due, on the onehand, to the polymer layers dissolving superficially, thus forming aslushy and sticky film, and, on the other hand, to the administrationforms adhering to the palate upon contact with the oral mucosa becauseof the pressure gradient from the upper side to the lower side of thepalate.

The property of these film-shaped administration forms of sticking tothe palate and other surfaces of the oral mucosa may cause an unpleasantsensation in the persons concerned or in the patients, i.e. the“mouthfeel” caused by the wafers is unpleasant or disturbing andtherefore in need of improvement.

SUMMARY OF THE INVENTION

An object of the present invention is to provide a film-shapedpreparation of the afore-mentioned type which has the known advantagesof quickly disintegrating administration forms but which at the sametime has improved disintegration properties resulting in an acceleratedactive substance release.

It is an additional object to reduce the tendency of adhering orsticking to the oral mucosa, so that an improved “mouthfeel” results ifthe preparation is used as an oral administration form.

A further object is to indicate processes by means of which film-shapedpreparations having the aforementioned improved properties may beobtained.

The objects of the present invention are surprisingly achieved byproviding a film-shaped preparation which is disintegratable in anaqueous media and contains at least one water-soluble polymer and whichadditionally contains one or two components that produce a gas uponaction of moisture, being in the presence of an aqueous medium or if achange in temperature occurs. This gas is released from the preparationif it is placed in the oral cavity, for example, and comes into contactwith saliva. The formation of gas bubbles during oral intake of afilm-shaped preparation (“wafer”) strongly affects the internalstructure of the wafer and causes it to rapidly disintegrate into aplurality of fragments. The wafer is thus virtually blown up by the gasbubbles forming in its interior. This results in an abrupt increase inthe available surface, which leads to an accelerated release of activesubstance.

In addition, the fact that gas bubbles escape at the surfaces of thewafer prevents the wafer from sticking to the mucosa. This in turnassists the supply of further liquid to both sides of the wafer. Bycontrast, in the case of the system adhering to the mucosa, as may occurin conventional wafers, only one side would be available for increasedliquid absorption.

In the case of oral application of the inventive wafer the escape of gasbubbles at the surfaces of the wafer in addition causes an improved“mouthfeel” since the wafer cannot adhere to the oral mucosa or tonguebut is continuously being separated from the mucosa by the bursting ofthe bubbles.

The object is furthermore achieved by the production processes describedin claims 13 to 16. Said claims enable the production of film-shapedpreparations according to the main claim which are disintegratable inaqueous media. An essential advantage of these methods is that duringthe production of the preparations it is possible to add gas-formingcomponents which can be activated by water or moisture, without theoccurrence of premature gas formation while the preparation is beingmanufactured.

DETAILED DESCRIPTION OF THE INVENTION

The preparations according to this invention are flat-shaped filmscontaining at least one water-soluble polymer. The water-solublepolymer(s) form(s) the basic structure, also called a matrix, of thepreparation. The composition of the matrix may further compriseauxiliary substances of a very different type by means of which thechemical and physical properties of the films are additionallyinfluenced. The weight content of the water-soluble polymer(s) ispreferably in the range of 10 to 95%-wt, especially preferably in therange of 15 to 70%-wt, in each case relative to the entire preparation(dry matter).

The matrix-forming polymer components used for this purpose arewater-soluble or at least partially water-soluble; they may bethermoplastic or non-thermoplastic. In the manufacture of thefilm-shaped preparations, thermoplastic formulations can be extrudedunder heat, whereas non-thermoplastic polymers can be extruded ashigh-viscous solutions.

Partial water-solubility is understood to mean the property of a largenumber of polymers of being swellable in water or in aqueous media. Thewater molecules in this case enter the polymer material slowly, whichresults in swelling and the formation of a gel. Subsequentdisintegration of the swollen gel to a true solution does not occur.This is true, in particular, with polymers of very high molecular weightor with cross-linked polymers.

The following polymers may be used for this purpose: polyvinyl alcohol(PVA), polyethylene oxide, copolymer of methyl vinyl ether and maleicacid, cellulose derivatives such as hydroxypropyl methyl cellulose(HPMC), hydroxypropyl cellulose (HPC), sodium-carboxymethyl cellulose(NaCMC), methyl cellulose (MC), hydroxyethyl cellulose (HEC),hydroxypropyl ethyl cellulose (HPEC), starch and starch derivatives,gelatins, polyvinyl pyrrolidone (PVP), gum arabic, pullulan oracrylates. Mixtures of two or more of the aforementioned polymers mayalso be used.

As auxiliary substances, which are in principle known to those skilledin the art, it is possible to use substances from the following groups:Fillers such as SiO₂; colorants such as quinoline yellow or TiO₂;disintegrants, respectively wicking agents, which draw water into thematrix and explode the matrix from within, e.g. aerosil; emulsifierssuch as Tween (polyethoxylated sorbitan fatty acid ester), Brij(polyethoxylated fatty alcohols); sweeteners such as aspartame, sodiumcyclamate and saccharine; softeners such as PEG (polyethylene glycol) orglycerol; preservatives such as, for example, sorbic acid or its salts.The content of these additives may preferably amount to up to 30%-wt, inparticular 1 to 20%-wt, each relative to the entire preparation.

Components which upon action of moisture or in the presence of anaqueous medium or in the case of a change in temperature produce a gasare in principle known to those skilled in the art. Preferably, thefilm-shaped preparations according to the present invention contain oneor more gas-forming component(s) selected from the group comprisingcarbonates, especially sodium carbonate, ammonium carbonate, magnesiumcarbonate, potassium carbonate and hydrogen carbonate, especially sodiumhydrogen carbonate, and acids, especially carboxylic acids such ascitric acid, malic acid, acetic acid, lactic acid, fumaric acid,gluconic acid, tartaric acid, as well as acid regulators, especiallysalts of acetic acid, sodium dihydrogen phosphate or disodium hydrogenphosphate, sodium tartrate, sodium ascorbate.

Gas formation is preferably caused by combining two or more components,especially by combining an alkaline earth carbonate or alkaline metalcarbonate or alkaline metal hydrogen carbonate with a carboxylic acid.Suitable carbonates or hydrogen carbonates are, in particular, sodiumhydrogen carbonate, sodium carbonate, potassium carbonate and potassiumhydrogen carbonate. Carboxylic acids which may be used are citric acid,malic acid, acetic acid, lactic acid, fumaric acid, gluconic acid andtartaric acid. A combination of sodium hydrogen carbonate with citricacid is especially preferred.

The proportion of the gas-forming component(s) may be up to 70%-wt,relative to the dry matter of the preparation; preferably, the contentis in the range from 5 to 60%-wt.

In the case of the above-mentioned gas-forming components, the gasformed upon action of an aqueous medium is carbon dioxide. This,however, does not exclude the possibility of another gas, e.g. nitrogen,forming when a different gas-forming compound or a mixture of compoundsis used. If the gas formed in the presence of water or an aqueous mediumis CO₂, this results in a further advantage of the inventive film-shapedadministration forms in that there is an improved absorption of theactive substance in the body. According to a preferred embodiment, thepreparations of the invention are characterized by forming an acidicenvironment in the presence of water or of an aqueous medium.

Apart from the above-mentioned components involved in the formation ofthe gas, the film-shaped preparations may additionally contain one ormore acid regulators. Suitable for this purpose are particularly saltsof acetic acid, sodium dihydrogen phosphate or disodium hydrogenphosphate, sodium tartrate and sodium ascorbate.

Activation of the gas formation preferably takes place under action ofwater, moisture or an aqueous medium. The film-shaped preparations mayfurthermore be configured such that gas formation is activated by achange in the thermal conditions, for instance if a film-shapedpreparation is taken orally and in the process is heated under theinfluence of the body heat (e.g. if its temperature rises to above 25 to35° C.). Gas formation by thermal activation is achieved by usingblowing agents, amongst which are ammonium carbonate, ammonium hydrogencarbonate, hartshorn salt (a mixture of ammonium carbonate, ammoniumhydrogen carbonate and ammonium carbamate), as well as hydrogencarbonate (sodium hydrogen carbonate, potassium hydrogen carbonate) inmixture with acid phosphates, acid pyrophosphates, citric acid ortartaric acid.

Another possibility which may be advantageous is activating the gasformation by a change in the pH value, for example after oraladministration of a film-shaped preparation. The access of moisture uponcontact with saliva enables the reaction between the gas-formingcomponents (carbonate and/or hydrogen carbonate on the one hand, andacid component on the other). The CO₂-releasing reaction is due to anacidification (pH activation) of the carbonate or hydrogen carbonatecomponent.

In the context of the present invention “aqueous media” is understood tomean, in particular, water, aqueous solutions, suspensions, dispersions,aqueous solvent mixtures as well as physiological liquids or body fluids(e.g. secretions of the body, saliva, mucus).

Due to their gas forming capacity, the film-shaped preparationsaccording to the present invention stand out for their improveddisintegration properties. These preparations are preferably configuredas rapidly disintegrating films, that is, they have disintegration timesin the range from 1 s to 5 min, preferably in the range from 1 s to 1min, especially preferably in the range from 1 s to 30 s.

The film-shaped preparations may have a thickness in the range from 5 μmto 3 mm, preferably between 10 μm and 1 mm, and particularly preferablybetween 20 μm and 500 μm.

The film-shaped preparations according to one embodiment of the presentinvention generally have a mono-layer structure. According to analternative embodiment, the preparations may be made up of at least twolayers connected with each other.

In one particular embodiment it is provided that the film-shapedpreparations are swellable in water or in aqueous media. This isachieved by providing a content of one or more swellable substances, forexample from the group comprising the hydrophile polyacrylates,hydrophile polymethacrylates, anionic or cationic hydrogels, agar,carboxymethyl cellulose, methyl cellulose, tragacanth, gelatine, andswellable ion exchange resins.

The film-shaped preparations are advantageously suitable for use asadministration forms for administering pharmaceutical substances. Forthis reason, it is provided in a preferred embodiment that such apreparation contains a pharmaceutical active substance or a combinationof two or more pharmaceutical active substances. The active substance(s)may be present in dissolved, dispersed, suspended or emulsified form.

Optionally, further releasable substances may be contained, e.g.flavouring or sweetening substances.

Suitable as active substance are, without reservation, those substanceswhich have a therapeutic effect in humans or animals. These mayoriginate from the following groups: agents for treating infections;virostatics; analgesics such as fentanyl, sufental, buprenorphine;anaesthetics; anorectics; active substances for treating arthritis andasthma, such as terbutaline; anticonvulsives; antidepressants;antidiabetics; antihistaminics; anti-diarrhoeal agents; agents againstmigraine; agents against itching, nausea and retching, motion andseasickness, such as scopolamine and ondansetron; antineoplastic agents;anti-Parkinson agents; antipsychotic agents; antipyretics;antispasmodics; anticholinergics; agents against ulcer, such asranitidine; sympathomimetics; calcium channel blockers such asnifedipine; beta blockers; beta-agonists, such as dobutamine andritodrine; antiarrhythmics; antihypertensive agents such as atenolol;ACE inhibitors such as enalapril; benzodiazepine agonists such asflumazenil; coronary, peripheral and cerebral vasodilators; substancesstimulating the central nervous system; hormones; hypnotics;immunosuppressing agents; muscle relaxants; prostaglandins; proteins,peptides; psychostimulants; sedatives; tranquilizers.

Suitable active substances are further found in the active substancegroups of the parasympatholytics (e.g. scopolamine, atropine,berlactyzine), of the parasympathomimetics, of the cholinergics (e.g.physostigmine, nicotine), the neuroleptics (e.g. chloropromazine,haloperidol), the monoamine oxidase inhibitors (e.g. tranylcypromine,selegiline), the sympathomimetics (e.g. ephedrine,D-nor-pseudoephedrine, salbutamol, fenfluramine), the sympatholytics andanti-sympathotonics (e.g. propranolol, timolol, bupranolol, clonidine,dihydroergotamine, naphazoline), the anxiolytics (e.g. diazepam,triazolam), the local anaesthetics (e.g. lidocaine), the centralanalgesics (e.g. fentanyl, sufentanil), the antirheumatics (e.g.indomethacin, piroxicam, lornoxicam), the coronary therapeutics (e.g.glycerol trinitrate, isosorbide dinitrate), the estrogens, gestagens andandrogens, the anti-histaminics (e.g. diphenhydramine, clemastin,terfenadine), the prostaglandin derivatives, the vitamins (e.g. vitaminE, cholecalciferol), the cytostatics and the cardioactive glycosidessuch as digitoxin and digoxin, for example.

The film-shaped preparations according to the invention may also be usedfor releasing one or more flavouring substances such as menthol or lemonflavour in the oral cavity. The flavouring substance(s) may, however,also be present in the preparation in combination with one or morepharmaceutical active substances.

The active substance content or the content of flavouring agent(s) ispreferably 0.1 to 50%-wt, with particular preference 1 to 25%-wt, ineach case relative to the dry matter of a film-shaped preparation.

The invention further comprises processes enabling the manufacture offilm-shaped preparations which are disintegratable in aqueous media andwhich contain gas-forming components and produce a gas under action ofmoisture or in the presence of an aqueous medium.

The processes according to the present invention are based on the basicprinciple, according to which, a coating compound is first preparedwhich contains matrix polymer(s), gas-forming substance(s), activeagent(s), and/or flavouring agent(s), and optionally further auxiliarysubstances. The coating compound is subsequently coated onto a supportand then dried.

In the manufacture of the inventive preparations it must be taken intoconsideration that in the manufacture of water-soluble (orwater-disintegratable) films, as a rule, water or an aqueous medium isused as solvent. Since the gas-forming components are activated by wateror moisture, the desired gas-forming reaction would occur prematurelyduring the production of a coating compound which contains thewater-soluble matrix polymers and the gas-forming components.

In accordance with the invention, this problem can be solved by means ofthe measures described below:

According to a first process of production according to the invention,it is provided that the production of the coating compound whichcontains the components of the preparation including the gas-formingcomponent(s) is carried through by dissolving or suspending thecomponents in a solvent or a suspending agent which is substantiallyfree from water, e.g. ethanol. This prevents the gas forming reactionfrom being triggered already during the production of the coatingcompound. After coating and drying, a water-soluble film remains whichshows gas formation upon contact with moisture and exhibits the desiredproperties.

“Substantially free from water” means that the water content is lessthan 8%-wt, preferably less than 5%-wt, and particularly preferably lessthan 1%-wt.

A second inventive process of production provides that the production ofthe coating compound containing the components of the preparationincluding the gas-forming component(s) is carried through by melting thecomponents. Subsequently, the molten coating compound is extruded onto asupport (carrier layer), preferably using a slot die. The cooled film isthen available for further processing. In this process variant,thermoplastic water-soluble polymers or polymer mixtures are used asmatrix-forming polymers. Since no water is used in this process, apremature activation of the gas formation is not possible.

A further possibility of producing film-shaped preparations having theclaimed properties is to initially produce two films from two coatingcompounds and subsequently combining the films, each coating compoundcontaining only a single one of the components necessary for theformation of the gas. For example, an aqueous polymer solution withsodium hydrogen carbonate and a further aqueous polymer solution withcitric acid are prepared first, and one water-soluble film each isproduced from these solutions by spreading these masses onto respectiveprocess films serving as support (e.g. polyester film, polyethylene filmor metal foil) and subsequent drying.

Since both components have to be present to activate the gas formation,no premature gas formation occurs during the production of the coatingcompounds, even if water or aqueous media are used as solvent orsuspending agent. The gas-forming process can thus not take place sincethe components necessary for gas formation are initially present inseparate films. Subsequently, the two films are united—e.g. bylaminating—such that one film results. Only after the application hastaken place (e.g. oral administration) does the film-shaped preparationabsorb water and the two gas-forming compounds come into contact witheach other, thus triggering the gas formation.

This production process comprises the following steps: First, a firstcoating compound is produced which contains a first gas-formingcomponent and further components of the film-shaped preparation. Thiscan be done by dissolving, suspending or dispersing said components inan aqueous solvent or suspending agent. A second coating compound isproduced in an analogous fashion; this coating compound contains asecond gas-forming component and further components of the film-shapedpreparation. The first and second components are reaction partnersnecessary for a gas-forming reaction. Each of the two coating compoundsis spread on a support and dried, thus forming a first and a secondfilm. The two films are combined by laminating one film on the other.

A fourth inventive production process makes use of the measure ofproviding at least one of the gas-forming components, or a mixture ofthe gas-forming components, in micro-encapsulated form during theproduction of the coating compound(s). Such encapsulation prevents thegas-forming reaction during the preparation of the compound. Only upon,for example, oral intake of the film—under the conditions present in theoral cavity such as pH value or body temperature—will the gas-formingreaction be activated. Suitable processes and auxiliary substances formicroencapsulating particles are known to those skilled in the art.

According to this process, a coating compound is prepared which containsthe components of the preparation including the gas-forming components,with at least one of the gas-forming components being present inmicroencapsulated form. The coating compound can be prepared bydissolving, suspending or dispersing the components in a solvent or asuspending agent. As activation of the formation of the gas is preventedby the microencapsulation, it is also possible to use aqueous media assolvents or suspending agents in this process. Thereafter, the coatingcompound is spread on a support and dried.

The film-shaped, disintegratable preparations according to the inventionare advantageously suitable for use as administration forms foradministering pharmaceutical active substances for therapeutic purposes,especially for oral, rectal or vaginal administration.

The invention will be illustrated by means of the following examples ofembodiments:

EXAMPLE 1

EXAMPLE 1 Proportion Dry matter No. Component %-wt 1 Ethanol 2 PVP 33% 3Citric acid 20% 4 NaHCO₃ 35% 5 Menthol  7% 6 Aspartame  5%

EXAMPLE 2

EXAMPLE 2 Proportion Dry matter No. Component %-wt 1 Ethanol 2 HPC 33% 3Citric acid 20% 4 NaHCO₃ 30% 5 Lemon flavour 12% 6 Aspartame  5%

Preparation of the compounds of Examples 1 and 2: No. 1 is providedfirst and then No. 2 is added thereto while stirring such that a 15%polymer solution results. Subsequently, Nos. 3, 5 and 6 are added andstirred until the mass is homogenous, thereafter No. 4 is added and thisis stirred until the mass is homogenous. The mass is spread as a thinfilm on a process film and dried for 15 min at 60-80° C. The dried filmis then separated into wafers.

What has been described above are preferred aspects of the presentinvention. It is of course not possible to describe every conceivablecombination of components or methodologies for purposes of describingthe present invention, but one of ordinary skill in the art willrecognize that many further combinations and permutations of the presentinvention are possible. Accordingly, the present invention is intendedto embrace all such alterations, combinations, modifications, andvariations that fall within the spirit and scope of the appended claims.

1. A process for producing a film-shaped preparation for administrationof substances to the human or animal body, said preparation beingdisintegratable in aqueous media and containing at least onewater-soluble polymer and at least one gas-forming component whichproduces a gas upon action of moisture, being in the presence of anaqueous medium or by a temperature change, comprising the steps of:preparing a coating compound which contains the components of thepreparation including said at least one gas-forming component bydissolving or suspending the components in a solvent or suspending agentthat is substantially free from water; spreading said coating compoundon a support; and drying said support.
 2. The process according to claim1, wherein said at least one gas-forming component is selected from thegroup consisting of carbonates, acids and acid regulators.
 3. Theprocess according to claim 2, wherein said at least one gas-formingcomponent is a combination of at least one first component and at leastone second component wherein said at least one first component is acarboxylic acid and said at least one second component is selected fromthe group consisting of sodium hydrogen carbonate, sodium carbonate,potassium carbonate and potassium hydrogen carbonate.
 4. The processaccording to claim 1, further comprising the step of the adding at leastone pharmaceutical active substance to said preparation.
 5. The processaccording to claim 1, further comprising the step of adding a flavouringagent to said preparation.
 6. A film-shaped preparation disintegratablein aqueous media, for administration of substances to the human oranimal body, containing at least one water-soluble polymer, saidpreparation containing at least one gas-forming component able toproduce a gas upon action of moisture, being in the presence of anaqueous medium or by a temperature change.
 7. A film-shaped preparationdisintegratable in aqueous media, for administration of substances tothe human or animal body, containing at least one water-soluble polymer,said preparation containing at least one gas-forming component able toproduce a gas upon action of moisture, being in the presence of anaqueous medium or by a temperature change, wherein at least one of saidat least one gas-forming component is is in a microencapsulated form. 8.A film-shaped preparation disintegratable in aqueous media, foradministration of substances to the human or animal body, containing atleast one water-soluble polymer, said preparation containing at leastone gas-forming component able to produce a gas upon action of moisture,being in the presence of an aqueous medium or by a temperature change,wherein said preparation has two film layers connected to each other,the first film layer containing a first gas-forming component andfurther components of the film-shaped preparation, and the second filmlayer containing a second gas-forming component and further componentsof the film-shaped preparation, wherein said first and secondgas-forming components are reaction partners of a gas-forming reaction.9. The preparation according to claim 7, wherein said at least onegas-forming component is selected from the group consisting ofcarbonates, acids and acid regulators.
 10. The preparation according toclaim 9, wherein said gas-forming components comprise a combination ofat least one first component and at least one second component, whereinsaid at least one first component is a carboxylic acid, and said atleast one second component is selected from the group consisting ofsodium hydrogen carbonate, sodium carbonate, potassium carbonate andpotassium hydrogen carbonate.
 11. The preparation according to claim 6,wherein said preparation produces CO₂ or N under action of water, anaqueous medium or moisture.
 12. The preparation according to claim 6,wherein said preparation produces an acid environment in the presence ofwater.
 13. The preparation according to claim 6, wherein saidpreparation disintegrates in the presence of water or an aqueous mediumwithin 1 s to 5 min.
 14. The preparation according to claim 6, whereinsaid preparation is swellable in aqueous media.
 15. The preparationaccording to claim 6, wherein said preparation further contains at leastone pharmaceutical active substance.
 16. The preparation according toclaim 6, wherein said preparation further contains a flavouring agent.17. The preparation according to claim 6, wherein said preparationcomprises at least two layers.
 18. The preparation according to claim 6,wherein said preparation has a thickness between 5 μm and 3 mm.
 19. Thepreparation according to claim 6, wherein said preparation is anadministration form selected from the group consisting of an oraladministrative form, a rectal administrative form and a vaginaladministrative form for administration of pharmaceutical active agents.20. The process according to claim 2, wherein said carbonates areselected from the group consisting of sodium carbonate, ammoniumcarbonate, magnesium carbonate, potassium carbonate, and hydrogencarbonate, said acids are selected from the group consisting of citricacid, malic acid, acetic acid, lactic acid, fumaric acid, gluconic acidand tartaric acid, and said acid regulators are selected from the groupconsisting of salts of acetic acid, sodium dihydrogen phosphate,disodium hydrogen phosphate, sodium tartrate and sodium ascorbate. 21.The process according to claim 20, wherein said hydrogen carbonate issodium hydrogen carbonate.
 22. The process according to claim 3, whereinsaid carboxylic acid is selected from the group consisting of citricacid, malic acid, acetic acid, lactic acid, fumaric acid, gluconic acidand tartaric acid.
 23. The process according to claim 5, wherein saidflavouring agent is menthol.
 24. A process for producing a film-shapedpreparation for administration of substances to the human or animalbody, said preparation being disintegratable in aqueous media andcontaining at least one water-soluble polymer and at least onegas-forming component which produces a gas upon action of moisture,being in the presence of an aqueous medium or by a temperature change,comprising the steps of: preparing a first coating compound whichcontains a first gas-forming component and further components of thefilm-forming preparation by dissolving or suspending said components inan aqueous solvent or suspending agent; preparing a second coatingcompound which contains said first gas-forming component and furthercomponents of the film-shaped preparation by dissolving or suspendingsaid components in an aqueous solvent or suspending agent, said firstand said second components being reaction partners of a gas-formingreaction; spreading the first coating compound on a support; drying saidsupport to form a first film; spreading the second coating compound on asupport; drying said support to form a second film; and laminating saidfirst film and said second film onto each other.
 25. The processaccording to claim 24, wherein said at least one gas-forming componentis selected from the group consisting of carbonates, acids and acidregulators.
 26. The process according to claim 25, wherein saidcarbonates are selected from the group consisting of sodium carbonate,ammonium carbonate, magnesium carbonate, potassium carbonate, andhydrogen carbonate, said acids are selected from the group consisting ofcitric acid, malic acid, acetic acid, lactic acid, fumaric acid,gluconic acid and tartaric acid, and said acid regulators are selectedfrom the group consisting of salts of acetic acid, sodium dihydrogenphosphate, disodium hydrogen phosphate, sodium tartrate and sodiumascorbate.
 27. The process according to claim 26, wherein said hydrogencarbonate is sodium hydrogen carbonate.
 28. The process according toclaim 24, wherein said at least one gas-forming component is acombination of at least one first component and at least one secondcomponent, wherein said at least one first component is a carboxylicacid, and said at least one second component is selected from the groupconsisting of sodium hydrogen carbonate, sodium carbonate, potassiumcarbonate and potassium hydrogen carbonate.
 29. The process according toclaim 28, wherein said carboxylic acid is selected from the groupconsisting of citric acid, malic acid, acetic acid, lactic acid, fumaricacid, gluconic acid and tartaric acid.
 30. The process according toclaim 24, further comprising the step of the adding at least onepharmaceutical active substance to said preparation.
 31. The processaccording to claim 24, further comprising the step of adding aflavouring agent to said preparation.
 32. The process according to claim31, wherein said flavouring agent is menthol.
 33. A process forproducing a film-shaped preparation for administration of substances tothe human or animal body, said preparation being disintegratable inaqueous media and containing at least one water-soluble polymer and atleast one gas-forming component which produces a gas upon action ofmoisture, being in the presence of an aqueous medium or by a temperaturechange, or comprising the steps of: preparing a coating compound whichcontains the components of the preparation including said at least onegas-forming component by dissolving or suspending the components in asolvent or a suspending agent, wherein at least one of said at least onegas-forming component is present in a microencapsulated form; spreadingsaid coating compound on a support; and drying said support.
 34. Theprocess according to claim 33, wherein said at least one gas-formingcomponent is selected from the group consisting of carbonates, acids andacid regulators.
 35. The process according to claim 34, wherein saidcarbonates are selected from the group consisting of sodium carbonate,ammonium carbonate, magnesium carbonate, potassium carbonate, andhydrogen carbonate, said acids are selected from the group consisting ofcitric acid, malic acid, acetic acid, lactic acid, fumaric acid,gluconic acid and tartaric acid, and said acid regulators are selectedfrom the group consisting of salts of acetic acid, sodium dihydrogenphosphate, disodium hydrogen phosphate, sodium tartrate and sodiumascorbate.
 36. The process according to claim 35, wherein said hydrogencarbonate is sodium hydrogen carbonate.
 37. The process according toclaim 33, wherein said at least one gas-forming component is acombination of at least one first component and at least one secondcomponent, wherein said at least one first component is a carboxylicacid, and said at least one second component is selected from the groupconsisting of sodium hydrogen carbonate, sodium carbonate, potassiumcarbonate and potassium hydrogen carbonate.
 38. The process according toclaim 37, wherein said carboxylic acid is selected from the groupconsisting of citric acid, malic acid, acetic acid, lactic acid, fumaricacid, gluconic acid and tartaric acid.
 39. The process according toclaim 33, further comprising the step of the adding at least onepharmaceutical active substance to said preparation.
 40. The processaccording to claim 33, further comprising the step of adding aflavouring agent to said preparation.
 41. The process according to claim40, wherein said flavouring agent is menthol.
 42. The preparationaccording to claim 13, wherein said preparation disintegrates in thepresence of water or an aqueous medium within 1 s to 1 min.
 43. Thepreparation according to claim 42, wherein said preparationdisintegrates in the presence of water or an aqueous medium within 1 sto 30 s.
 44. The preparation according to claim 16, wherein saidflavouring agent is menthol.
 45. The preparation according to claim 18,wherein said preparation has a thickness between 10 μm and 1 mm.
 46. Thepreparation according to claim 45, wherein said preparation has athickness 20 μm and 500 μm.
 47. The preparation according to claim 9,wherein said carbonates are selected from the group consisting of sodiumcarbonate, ammonium carbonate, magnesium carbonate, potassium carbonate,and hydrogen carbonate, said acids are selected from the groupconsisting of citric acid, malic acid, acetic acid, lactic acid, fumaricacid, gluconic acid and tartaric acid, and said acid regulators areselected from the group consisting of salts of acetic acid, sodiumdihydrogen phosphate, disodium hydrogen phosphate, sodium tartrate andsodium ascorbate.
 48. The preparation according to claim 47, whereinsaid hydrogen carbonate is sodium hydrogen carbonate.
 49. Thepreparation according to claim 10, wherein said carboxylic acid isselected from the group consisting of citric acid, malic acid, aceticacid, lactic acid, fumaric acid, gluconic acid and tartaric acid. 50.The preparation according to claim 7, wherein said preparation producesCO₂ or N₂ under action of water, an aqueous medium or moisture.
 51. Thepreparation according to claim 7, wherein said preparation produces anacid environment in the presence of water.
 52. The preparation accordingto claim 7, wherein said preparation disintegrates in the presence ofwater or an aqueous medium within 1 s to 5 min.
 53. The preparationaccording to claim 52, wherein said preparation disintegrates in thepresence of water or an aqueous medium within 1 s to 1 min.
 54. Thepreparation according to claim 53, wherein said preparationdisintegrates in the presence of water or an aqueous medium within 1 sto 30 s.
 55. The preparation according to claim 7, wherein saidpreparation is swellable in aqueous media.
 56. The preparation accordingto claim 7, wherein said preparation further contains at least onepharmaceutical active substance.
 57. The preparation according to claim7, wherein said preparation further contains a flavouring agent.
 58. Thepreparation according to claim 57, wherein said flavouring agent ismenthol.
 59. The preparation according to claim 7, wherein saidpreparation comprises at least two layers.
 60. The preparation accordingto claim 7, wherein said preparation has a thickness between 5 μm and 3mm.
 61. The preparation according to claim 60, wherein said preparationhas a thickness between 10 μm and 1 mm.
 62. The preparation according toclaim 61, wherein said preparation has a thickness between 20 μm and 500μm.
 63. The preparation according to claim 7, wherein said preparationis an administration form selected from the group consisting of an oraladministrative form, a rectal administrative form and a vaginaladministrative form for administration of pharmaceutical active agents.64. The preparation according to claim 8, wherein said at least onegas-forming component is selected from the group consisting ofcarbonates, acids and acid regulators.
 65. The preparation according toclaim 64, wherein said carbonates are selected from the group consistingof sodium carbonate, ammonium carbonate, magnesium carbonate, potassiumcarbonate, and hydrogen carbonate, said acids are selected from thegroup consisting of citric acid, malic acid, acetic acid, lactic acid,fumaric acid, gluconic acid and tartaric acid, and said acid regulatorsare selected from the group consisting of salts of acetic acid, sodiumdihydrogen phosphate, disodium hydrogen phosphate, sodium tartrate andsodium ascorbate.
 66. The preparation according to claim 65, whereinsaid hydrogen carbonate is sodium hydrogen carbonate.
 67. Thepreparation according to claim 64, wherein said gas-forming componentscomprise a combination of at least one first component and at least onesecond component, wherein said at least one first component is acarboxylic acid, and said at least one second component is selected fromthe group consisting of sodium hydrogen carbonate, sodium carbonate,potassium carbonate and potassium hydrogen carbonate.
 68. Thepreparation according to claim 67, wherein said carboxylic acid isselected from the group consisting of citric acid, malic acid, aceticacid, lactic acid, fumaric acid, gluconic acid and tartaric acid. 69.The preparation according to claim 8, wherein said preparation producesCO₂ or N₂ under action of water, an aqueous medium or moisture.
 70. Thepreparation according to claim 8, wherein said preparation produces anacid environment in the presence of water.
 71. The preparation accordingto claim 8, wherein said preparation disintegrates in the presence ofwater or an aqueous medium within 1 s to 5 min.
 72. The preparationaccording to claim 71, wherein said preparation disintegrates in thepresence of water or an aqueous medium within 1 s to 1 min.
 73. Thepreparation according to claim 72, wherein said preparationdisintegrates in the presence of water or an aqueous medium within 1 sto 30 s.
 74. The preparation according to claim 8, wherein saidpreparation is swellable in aqueous media.
 75. The preparation accordingto claim 8, wherein said preparation further contains at least onepharmaceutical active substance.
 76. The preparation according to claim8, wherein said preparation further contains a flavouring agent.
 77. Thepreparation according to claim 76, wherein said flavouring agent ismenthol.
 78. The preparation according to claim 8, wherein saidpreparation comprises at least two layers.
 79. The preparation accordingto claim 8, wherein said preparation has a thickness between 5 μm and 3mm.
 80. The preparation according to claim 79, wherein said preparationhas a thickness between 10 μm and 1 mm.
 81. The preparation according toclaim 80, wherein said preparation has a thickness between 20 μm and 500μm.
 82. The preparation according to claim 8, wherein said preparationis an administration form selected from the group consisting of an oraladministrative form, a rectal administrative form and a vaginaladministrative form for administration of pharmaceutical active agents.